title: Molecular basis for the expression of major vault protein induced by hyperosmotic stress in SW620 human colon cancer cells.
abstract: Major vault protein (MVP) is identical to lung resistance-related protein (LRP), which is the major component of vaults. Vaults are considered to play a protective role against xenobiotics and other types of stress. In a previous study, we reported that the expression levels of MVP in SW620 human colon cancer cells were increased in hypertonic culture medium with sucrose. However, the molecular mechanism behind the induction of MVP expression by osmotic stress has not yet been elucidated. Therefore, in the present study, we investigated the mechanism behind the induction of MVP expression by osmotic stress. Under hyperosmotic stress conditions, the ubiquitination of specificity protein 1 (Sp1) decreased, Sp1 protein levels increased, its binding to the MVP promoter was enhanced, and small interfering RNA (siRNA) for Sp1 suppressed the induction of MVP expression. The inhibition of c-jun N-terminal kinase (JNK) by SP600125, a specific JNK inhibitor, decreased the expression of MVP and Sp1 under hyperosmotic conditions. Our data indicate that the stabilization and upregulation of Sp1 protein expression by JNK participate in the inhibition of the ubiquitination and degradation of Sp1, and thus in the induction of MVP expression under hyperosmotic conditions.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tajitsu
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ikeda
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mataki
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Che
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sumizawa
authors.forename: Mina
authors.initials: M
authors.lastname: Nitta
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Masatatsu
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Sho
authors.initials: S
authors.lastname: Tabata
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamada
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Furukawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009997:Osmotic Pressure; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D000099187:Major Vault Protein
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex; D016329:Sp1 Transcription Factor; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein